Organisms including the human body obtain energy through the breathing process, and about 2% of the oxygen inhaled during metabolism is converted to reactive oxygen species (ROS) known as “oxygen toxin.” The reactive oxygen species mean the oxygen containing a free radical (a generic term of atoms or molecules with unpaired electron), and generally includes lipid peroxide, lipid peroxy radical, peroxynitrite, etc. Such reactive oxygen species are known to be unstable and thus very reactive with the ambient substances to exert oxidative injuries to DNA having genetic information as well as proteins or lipid molecules in the cell, whereby ultimately fatal damage is exerted on the cell. On the other hand, in such cells of the immune system as macrophages or neutrophils, the production of reactive oxygen species is induced to play a useful role of killing pathogens that invade from the outside. Unlike in the above case and the recently recognized case wherein the reactive oxygen species play an important role in signal transduction inside the cell, the reactive oxygen species are generally recognized as causing damage to the cell and thus being harmful to organisms. Thus, in order to protect cells from the oxygen toxin, the cells themselves have antioxidants (e.g., Vitamin C, Vitamin E, small peptides such as glutathione) and antioxidant enzymes (e.g., catalase, superoxide dismutase [SOD], glutathione-dependent peroxidase [GPX], etc.).
Examples of diseases or metabolisms associated with the reactive oxygen species (ROS) or antioxidant enzymes are as follows:
1. Insulin-dependent diabetes is developed by the damage of pancreatic beta-cells, which is due to the abnormal expression of ROS.
2. Down syndrome, the subject of current clinical attention is known to be caused by the abnormality of the chromosome 21. In this case, SOD, an antioxidant enzyme, is abnormally expressed.
3. An antioxidant enzyme (catalase, glutathione-dependent peroxidase) analyzed in a cell of a progeria patient shows low enzyme activity.
4. Even in the process of converting normal cells to cancer cells, ROS is actively produced in the cells during the administration of several cancer-causing substances and irradiation.
5. Besides the above, ROS is known to be involved in atherosclerosis, Alzheimer's disease, ischemic disease, etc.
Some free radicals, reactive oxygen species and peroxides are produced during the metabolisms even in normal cells. However, the cells protect themselves against such harmful substances using antioxidant enzymes such as SOD, catalase, peroxidase, etc. as a defense system along with antioxidants such as Vitamin E, Vitamin C, glutathione, ubiquinone, uric acid, etc. When such a defense system has an abnormality or the production of reactive oxygen species exceeds the capacity of the defense system due to a variety of physical or chemical factors, however, oxidative stress is induced. If a person's disease is related to the imbalance between the oxidative stress and the antioxidative defense system in the body, theoretically the oxidative damage can be reduced or the further progress of the disease can be suppressed by adding an antioxidative substance. Thus, antioxidative functional substances such as free radical scavengers or substances inhibiting the production of peroxides are now widely used in the fields of polymers, foods, cosmetics, etc. They may also be used as an inhibitory or therapeutic agent for aging and various diseases caused by these oxides, which is based on the recent discovery that the reactive oxygen species are involved in physiological phenomena associated with the various diseases. Interest in the development of a therapeutic agent using them is increasing gradually, and the agent is actually being marketed as a health supplement in the U.S.A. with continuing popularity.
It has been demonstrated that oxidative stress is an important causative factor in inducing a variety of diseases including aging. Accordingly, the possibility of antioxidative functional substances having the ability to remove the reactive oxygen species as an agent for suppressing aging and for treating diseases is highly magnified. Thus, it is required to develop a new antioxidative functional substance that may have a function of treating aging caused by oxidative stress and a variety of diseases.
There are many antioxidants, but most of them are not effectively delivered to mitochondria and thus show a weak or little efficacy. This is why the delivery of antioxidants to mitochondria is very important in treating the above-mentioned diseases. In the case of the compound Mito Q, it was possible to be used as a therapeutic agent by conjugating coenzyme Q10 with a peptide targeting mitochondria.
On the other hand, such oxidative stress has been reported as the main mechanism of ischemic reperfusion injury. Ischemic diseases include ectomy, organ transplantation, embolization, myocardial infarction, stroke, etc.